Understanding of the neurophysiologic mechanisms by which noxious and non-noxious stimuli are perceived is imperative for the development of new drugs and techniques to treat pain. However, the mechanisms of transmission and perception of pain are not entirely understood and pain still is the most common reason why patients seek health care. Therefore, animal models of pain are necessary to further our understanding of the mechanisms of pain transmission. Currently available models to study transmission of pain use heat, pressure, or chemical stimulation to inflict pain. These models have contributed to many discoveries in the field but have limitations. Some of the limitations include the fact that heat and pressure can be associated with injury to animals, the stimuli can nonspecifically stimulate several types of nerve fibers (Aa-pressure, Aa-sharp pain, C-slow burning pain), and these stimuli can be associated with habituation learning. In order to study the mechanisms of the transmission of noxious stimuli, we developed a novel, non-injurious, neuro-specific nociception assay to study transmission of noxious stimulus via specific nerve fibers in a live system. We use a neuro-stimulator that is routinely used for the diagnosis of pain syndromes and neurologic diseases in humans. This neurostimulator delivers electrical stimuli to the skin at different frequencies and intensities and produces transient discomfort without producing injury. Each of the electrical frequencies used stimulate a specific type of pain fiber and allows for the measure of pain threshold for each type of pain fiber. In the model, we define vocalization as the pain avoiding behavior to the electrical stimulus and use it as the end point to measure current vocalization threshold for each of the pain fibers. Unlike currently used pain models that may produce some tissue-injury in order to induce pain, this assay is non-injurious, neuro-specific for each pain fiber, and adds an invaluable tool for the study of the mechanisms of pain. We completed pilot studies for the development of a non-injurious neuro-specific nociceptive assay in mice, developed normative values for the response to each frequency, and have fully developed software application to control the neuro-stimulator, and automated a large portion of the protocol. In addition, we are implementing upgrades to enable completely automated data collection and storage. We are now using the model to study the impact of aging as well as the role of neuronal nitric oxide in the transmission of noxious stimuli in specific nociceptive nerve fibers. Ongoing investigations will serve to further validate the model and demonstrate its value for studies of the mechanisms of pain. In addition, the assay serves as a valuable tool to study the pharmacodynamics of new therapeutic agents to treat pain.